Pioneering Precision Cardiovascular Medicine. (NASDAQ: MYOK) Corporate Presentation March 2018

Transcription

1 Pioneering Precision Cardiovascular Medicine (NASDAQ: MYOK) Corporate Presentation March 2018

2 Forward-Looking Statements Statements we make in this presentation may include statements which are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements regarding the clinical and therapeutic potential of mavacamten (formerly MYK-461) and MYK-491, the Company's ability to continue to advance mavacamten in the PIONEER-HCM study and MYK-491 in its Phase 1 study in healthy volunteers, the Company s expectations with respect to the release of data from these studies and the timing thereof, the Company's ability to initiate its planned Phase 3 EXPLORER-HCM study of mavacamten in symptomatic ohcm and its planned Phase 2 MAVERICK-HCM study of mavacamten in nhcm and the timing thereof, the anticipated numbers of patients expected to be enrolled in these studies, the Company s ability to initiate its planned Phase 1b trial of MYK-491 in DCM patients and generate data therefrom, and the timing of these events, as well as the requirements for registration of the Company's product candidates and the Company s projected cash runway, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, risks associated with the development and regulation of our product candidates, as well as those set forth in our Quarterly Report on Form 10-Q for the quarter ended December 31, 2017, and our other filings with the SEC. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. 2

3 Rethinking Cardiovascular Disease MyoKardia is applying a precision medicine approach to the discovery and development of innovative, targeted medicines for cardiovascular diseases 3

4 Company Highlights Mavacamten: Moving into Phase 3, expanding potential indications - Patient dosing in pivotal Ph 3 EXPLORER-HCM study in ohcm planned for Q Robust improvements in function and symptoms seen in Ph 2 PIONEER-HCM study - Plan to initiate PIONEER-HCM OLE in Q Ph 2 MAVERICK-HCM study in 2 nd potential indication, nhcm, expected to initiate dosing in Q MYK-491: Phase 1b underway, potential in several DCM patient subtypes - First-in-human Ph 1 study successfully completed - Ph 1b trial in DCM currently enrolling patients, topline expected in 2H Patient dosing in Ph 2 planned for 2H 2018 Discovery and Preclinical: Emerging pipeline of new targeted cardiovascular therapeutics - Applying precision medicine approach and cardiac muscle expertise - Clinical learnings informing drug discovery and preclinical programs 4

5 Other Patient Segments Mavacamten: nhcm Other Patient Segments Other Patient Segments Other Patient Segments Addressing Large Patient Populations Segmented into Smaller, Well-Defined Subgroups Total U.S. heart failure population of ~6 million Hypertrophic Cardiomyopathy (630,000) Dilated Cardiomyopathy (900,000) Obstructive HCM (410,000) Nonobstructive HCM (220,000) Genetic DCM (360,000) Idiopathic DCM (540,000) Mavacamten: Symptomatic ohcm (Orphan Drug Designation) MYK-491: Genetic DCM population(s) MYK-491: Other Targeted Indications 5 NOTE: All figures approximate. Reflect estimated diagnosed and undiagnosed totals.

6 Portfolio of Potential First-in-Class Cardiovascular Targeted Therapies Preclinical Phase 1 Phase 2 Phase 3 US rights Ex-US Mavacamten Symptomatic, obstructive HCM Non-obstructive HCM MYK-491 DCM (1) HCM-2 DCM-2 LUS-1 (1) MyoKardia retains co-commercialization option to MYK-491 in the U.S. 6 Anticipated development progress in 2018 MyoKardia Sanofi

7 Symptomatic Obstructive HCM: Our First Mavacamten Indication The ohcm Heart Autosomal dominant genetic disease Characterized by dynamic LVOT obstruction, excess contractility Thickened heart muscle is able to hold less blood and may be unable to relax Burden of Disease 65,000 of 100,000 diagnosed U.S. HCM patients have obstructive disease (1)(2) 16% diagnosis rate (3) U.S. Prevalence ~1:500 or > 630,000 (1) Chronic, progressive, debilitating Shortness of breath, chest pain, disabling heart failure, stroke Leading cause of sudden cardiac death in children and young adults Standard of Care Current disease management inadequate and not disease-specific Beta-blockers, calcium channel blockers Surgical & interventional options 7 1. AJC 2016: 100,000 patients currently seeking treatment for their HCM in the US 2. Circ 2006: 2/3 of HCM patients have obstructed disease 3. Maron et al., AJC 2016

8 Phase 2 Phase 3 Phase 2 Phase 1 Mavacamten Development Program Study Population Description Milestone SAD MAD SAD Healthy adults Safe and generally well tolerated Proof-of-mechanism achieved: reduction of cardiac hypercontractility HCM 3 Phase 1 studies completed PIONEER- HCM Cohort A PIONEER- HCM Cohort B ohcm β-blocker washout ohcm Proof-of-concept achieved: LVOT gradient reductions Improved patient symptoms across several measures Suggests starting dose and dose adjustment for Phase 3 N = 21 Treatment duration = 12 weeks Data reported Q Data reported Q EXPLORER- HCM ohcm Randomized, placebo-controlled pivotal trial to assess efficacy N = Study duration = 6 months +/- Plan to initiate patient dosing Q MAVERICK- HCM nhcm Assess safety, efficacy and determine optimal dosing N = 60 Study duration = 7 months Plan to initiate patient dosing Q PIONEER-HCM - Cohort B PIONEER-HCM Cohort A Long-Term PIONER Extension EXPLORER-HCM Planned NDA Filing Phase 1 studies Long-Term EXPLORER Extension MAVERICK-HCM 9 Today

9 PIONEER-HCM: Baseline Characteristics Largely Similar Across Dose-Ranging Cohorts Trial Design Baseline Characteristics Cohort A Cohort B Cohort A Cohort B Dose Dose adjustment criteria 10mg, 15mg, 20mg Percentage decrease in LVEF from baseline 2mg, 5mg Percentage decrease in resting LVOT gradient from baseline N Age (years) mean (min-max) 56 (22 70) 57 (22 71) Sex, % male 64% 50% NYHA Class 64% Class II; 36% Class III 50% Class II; 50% Class III Concomitant β- blockers, N (%) 0 (0) 9 (90) Mavacamten Study Drug Parameter (Mean ±SD) Cohort A Cohort B Starting Dose Adjusted Dose Resting LVEF (%) 70 ± 7 75 ± 5 Exercise LVEF (%) 76 ± 8 76 ± 8 Dose Adjustment Resting LVOT Gradient (mm Hg) Exercise LVOT Gradient (mm Hg) 60 ± ± ± ± 43 Peak VO 2 (ml/kg/min) 20.7 ± ± 4.6 9

10 Demonstrated Efficacy and Safety Across a Broad Range of Mavacamten Doses Change, from baseline to W12 Mean ± SD p-value Mean ± SD p-value Cohort A Cohort B Post-exercise LVOT gradient (mmhg) -112 ± ± Resting LVOT gradient (mmhg) -55 ± ± Resting LVEF (%) -16 ± ± NYHA class -0.9 ± ± Peak VO2 (ml/kg/min) +3.5 ± ± Dyspnea numerical rating -3.1 ± ± Additional Observations Mavacamten was generally well tolerated - Most AEs were mild (80%) to moderate (19%) - Most AEs were deemed unrelated to mavacamten (79%) Effect of Beta Blockers No discernable impact on mavacamten s pharmacodynamics profile were observed with use of background beta blockers LVOT gradient, NYHA class, LVEF measures reverted towards baseline during fourweek washout period 10

11 mmhg mmhg PIONEER-HCM: Mavacamten Reduces LVOT Gradient Cohort A Post-Exercise LVOT Gradient (p=0.002) 1 Cohort B Post-Exercise LVOT Gradient (p=0.020) 2 Patient achieving a reduction in post-exercise LVOT gradient below hemodynamic significance (< 50 mmhg): - Cohort A: 10/10 - Cohort B: 4/10 Impact of gradient on symptoms and function confirms previous literature findings 1 Heitner, et al; HFSA Jacoby, et al; ACC

12 mmhg mmhg PIONEER-HCM: Mavacamten Reduces LVOT Gradient Cohort A Resting LVOT Gradient (p=0.006) 1 Cohort B Resting LVOT Gradient (p=0.004) 2 Patient achieving a reduction in post-exercise LVOT gradient below hemodynamic significance (< 50 mmhg): - Cohort A: 10/10 - Cohort B: 4/10 Impact of gradient on symptoms and function confirms previous literature findings 1 Heitner, et al; HFSA Jacoby, et al; ACC

13 PIONEER-HCM: Consistent Improvements in Function and Symptoms Observed Across Dose-Ranges: Peak VO 2 Cohort A Baseline Week 12 Change p-value Peak VO 2 (ml/kg/min) 20.7 ± ± ± VE/VCO ± ± ± Circulatory Power (mm Hg mlo2 kg 1 min 1) 3276 ± ± ± Heitner, et al; HFSA 2017 Cohort B Peak VO 2 (ml/kg/min) Baseline Week 12 Change p-value 19.4 ± ± ± VE/VCO ± ± ± Circulatory Power (mm Hg mlo2 kg 1 min 1) 2944 ± ± ± of 10 patients had an improvement in peak VO ml/kg/min (~10% increase) - 4 of these 5 were on β-blockers 13 Jacoby, et al; ACC 2018

14 PIONEER-HCM: Consistent Improvements in Function and Symptoms Observed Across Dose-Ranges: NYHA Class NYHA Classification Cohort A Mean change -0.9 (p=0.016) - 5 subjects with 1 class improvement - 2 subjects with 2 class improvement Cohort B Heitner, et al; HFSA 2017 Mean change -1.0 (p=0.004) - 8 subjects with 1 class improvement - 1 subject with 2 class improvement Jacoby, et al; ACC

15 PIONEER-HCM: Emerging Target Mavamcamten Concentration Range will Inform Starting Dose and Dose Adjustment in EXPLORER-HCM Mavacamten Concentrations vs. Provoked LVOT Jacoby, et al; ACC

16 Pivotal EXPLORER-HCM Study to Begin Dosing in Q Study Goal: Demonstrate Clinically-Meaningful Improvements in Symptoms Population Symptomatic ohcm (similar to PIONEER-HCM) Design Randomized, double-blind, placebo-controlled Study Size Approximately patients Treatment Key Endpoints Anticipated Milestones Daily oral dosing for ~6 months Dose adjustment based on physiologic response Post-exercise LVOT gradient Change in exercise capacity (peak VO 2 ) NYHA functional class LVEF Dyspnea symptom score NT-proBNP Regulatory update Q Initiate patient dosing in Q Subject to finalization

17 Non-Obstructive HCM: Potential Second Indication for Mavacamten The nhcm Heart Same underlying genetics as ohcm Characterized by excess contractility without a physical obstruction More uniformly thickened heart muscle is unable to relax and fill with blood normally Burden of Disease Standard of Care nhcm is estimated to make up onethird of HCM population (1)(2) Patients typically diagnosed after disease progression Chronic, debilitating symptoms Shortness of breath, chest pain, disabling heart failure, stroke Lacking therapeutic options No disease-specific therapeutics Beta blockers and diuretics may be used to improve symptoms Heart transplant option of last resort Alternate surgical options unavailable AJC 2016: 100,000 patients currently seeking treatment for their HCM in the US 2. Circ 2006: 2/3 of HCM patients generally are obstructed

18 MAVERICK-HCM Phase 2 Initiating in Q Study Goal: Demonstrate Safety, Tolerability and Evidence of Activity Across Additional Endpoints Population Symptomatic nhcm with preserved LVEF Design Study Size 60 patients at 35 sites Treatment Randomized, double-blind, placebo-controlled Three-arms: mavacamten doses targeting two plasma concentrations vs. placebo Daily oral doses for 16 weeks Dose adjustment at week 6 Primary Endpoint Safety and tolerability Additional Endpoints Anticipated Milestones Exercise capacity as measured by peak VO 2 LVEF PD & PK Quality of life, daily activity NT-proBNP (rest & exercise) Reversibility Initiate patient dosing Q

19 Portfolio of Potential First-in-Class Cardiovascular Targeted Therapies Preclinical Phase 1 Phase 2 Phase 3 US rights Ex-US Mavacamten Symptomatic, obstructive HCM Non-obstructive HCM MYK-491 DCM (1) HCM-2 DCM-2 LUS-1 (1) MyoKardia retains co-commercialization option to MYK-491 in the U.S. 19 Anticipated development progress in 2018 MyoKardia Sanofi

20 Dilated Cardiomyopathy (DCM): Devastating Disease with No Approved Therapies The DCM Heart Characterized by thin walls of left ventricle and hypocontractility Inadequate contraction and insufficient blood pumped by heart Burden of Disease ~ 900,000 DCM patients in the U.S., 40% with identified gene mutation Chronic, progressive, debilitating Shortness of breath, edema, fatigue Interference with daily activities Increased risk of sudden cardiac death and need for heart transplant Standard of Care No approved therapeutics to target underlying disease Nonspecific heart failure therapies Treatments for advanced disease complex and limited in availability & efficacy LVAD, transplant, palliative care 20

21 % Change from Baseline % Change from Baseline MYK-491 Improves Cardiac Function without Impairing Relaxation in Preclinical Models MYK-491: Designed to Improve Symptoms of Heart Failure MYK-491 is a cardiac myosin activator - Heart muscle protein mutations diminish systolic contraction Targets the biomechanical cause of DCM - Inadequate motor engagement Goals of treatment - Increase the extent of contraction - Minimal impact on diastole / relaxation - Potential for beneficial remodeling - Potential wider therapeutic index Preclinical Data Paced HF Dog Model LVOT-Velocity Time Integral Vehicle 1 mg/kg 3 mg/kg 5 mg/kg 0h 3h 6h Tau (Time Constant of Isovolumic Relaxation) Vehicle 1 mg/kg 3 mg/kg 5 mg/kg h 3h 6h 20

22 MYK-491 First-in-Human Safety Study Complete Study Goal: Demonstrate Tolerability, Inform Starting Dose for Ph 1b Phase 1 Clinical Trial of MYK-491 Design Population Endpoints Randomized, double-blind, placebo controlled Single ascending dose 64 healthy volunteers 48 subjects received 16 subjects received placebo Safety, tolerability, PK, PD Echocardiographic measures of effect on contractility Topline Results MYK-491 was well tolerated - Adverse events were benign and transient Increases in contractility observed at highest dose cohorts Phase 1b starting dose identified 22

23 MYK-491 Phase 1b in DCM Patients Underway Study Goal: Demonstrate Proof-of-Mechanism in Patients Design Phase 1b Randomized, double-blind, placebo controlled, Adaptive design Single ascending dose Population DCM patients with stable, moderate HF Endpoints Anticipated Milestones Safety, tolerability, PK, PD Echocardiographic measures of effect on contractility Results anticipated in 2H

24 Portfolio of Potential First-in-Class Cardiovascular Targeted Therapies Preclinical Phase 1 Phase 2 Phase 3 US rights Ex-US Mavacamten Symptomatic, obstructive HCM Non-obstructive HCM MYK-491 DCM (1) HCM-2 DCM-2 LUS-1 (1) MyoKardia retains co-commercialization option to MYK-491 in the U.S. 24 Anticipated development progress in 2018 MyoKardia Sanofi

25 Research Focus: Cardiac Muscle Contraction and Relaxation Cardiomyopathies Result from 3 Types of Cardiac Muscle Disruptions Normal Heart Hypertrophic Cardiomyopathy (HCM) Dilated Cardiomyopathy (DCM) Normal contraction Excessive contraction Impaired relaxation Inadequate contraction 25

26 Targeting Cardiac Muscle Proteins to Modulate Function Mavacamten and MYK-491: Myosin-actin cross bridge Myosin binding Myosin-actin protein C crossbridge Troponin α Tropomyosin T Troponin I Actin Pipeline programs: Validated genetic targets Myosin light chain β Myosin heavy chain 26

27 Integrated, Disease-Focused Approach Generating New Leads & Advancing to INDs Precision Medicine Research Select disease targets in causal pathway Identify patient populations most likely to benefit Physician/Patient Initiatives SHaRe HCM Cares App Affairs of the Heart events Symptoms and function endpoints Imaging biomarkers Digital health wearable Diagnosis Monitoring Clinical Experience 27

28 2018 Multiple Value-Creating Clinical Milestones 2018 Q Initiate MAVERICK- HCM study in nhcm Q Report data from PIONEER-HCM Cohort B Q Report data from Phase 1 study in healthy volunteers Q Initiate Phase 3 EXPLORER-HCM study Q Initiate PIONEER Open-label Extension 2H 2018 Preclinical & Discovery-stage Pipeline Update 2H 2018 Report data from Phase 1b in DCM patients 2H 2018 Initiate Phase 2 study for MYK-491 Mavacamten Milestone MYK-491 Milestone Q Initiate Phase 1b patient study Well resourced to execute Cash and investments as of Q = $276M Anticipate current cash + potential Sanofi payments will fund operations into

29 Thank You 29

30 The Obstructed HCM Heart Characterized by dynamic LVOT obstruction, excess contractility Thickened heart muscle is able to hold less blood and may be unable to relax HCM CARE 30

31 PIONEER-HCM (Cohort B): Low Doses of Mavacamten Lead to Clinically Meaningful Results While Preserving LVEF Change in resting LVEF Jacoby, et al; ACC